scholarly journals Incidence of Differentiation Syndrome Associated with Treatment Regimens in Acute Myeloid Leukemia: A Systematic Review of the Literature

2020 ◽  
Vol 9 (10) ◽  
pp. 3342
Author(s):  
Lucia Gasparovic ◽  
Stefan Weiler ◽  
Lukas Higi ◽  
Andrea M. Burden
Keyword(s):  
Adverse Drug Reaction ◽  
Clinical Trials ◽  
Acute Myeloid Leukemia ◽  
Drug Reaction ◽  
Myeloid Leukemia ◽  
Remission Induction ◽  
Comprehensive Overview ◽  
Treatment Regimens ◽  
Differentiating Agents ◽  
Acute Myeloid

Differentiation syndrome (DS) is a potentially fatal adverse drug reaction caused by the so-called differentiating agents such as all-trans retinoic acid (ATRA) and arsenic trioxide (ATO), used for remission induction in the treatment of the M3 subtype of acute myeloid leukemia (AML), acute promyelocytic leukemia (APL). However, recent DS reports in trials of isocitrate dehydrogenase (IDH)-inhibitor drugs in patients with IDH-mutated AML have raised concerns. Given the limited knowledge of the incidence of DS with differentiating agents, we conducted a systematic literature review of clinical trials with reports of DS to provide a comprehensive overview of the medications associated with DS. In particular, we focused on the incidence of DS reported among the IDH-inhibitors, compared to existing ATRA and ATO therapies. We identified 44 published articles, encompassing 39 clinical trials, including 6949 patients. Overall, the cumulative incidence of DS across all treatment regimens was 17.7%. Incidence of DS was notably lower in trials with IDH-inhibitors (10.4%) compared to other regimens, including ATRA and/or ATO (15.4–20.6%). Compared to other therapies, the median time to onset was four times longer with IDH-inhibitors (48 vs. 11 days). Treating oncologists should be mindful of this potentially fatal adverse drug reaction, as we expect the current trials represent an underestimation of the actual incidence.

scholarly journals LSD1/KDM1A inhibitors in clinical trials: advances and prospects

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Yuan Fang ◽  
Guochao Liao ◽  
Bin Yu
Keyword(s):  
Lung Cancer ◽  
Clinical Trials ◽  
Acute Myeloid Leukemia ◽  
Cancer Therapy ◽  
Myeloid Leukemia ◽  
Histone Demethylase ◽  
Mechanistic Studies ◽  
Drug Reactions ◽  
Comprehensive Overview ◽  
Acute Myeloid

AbstractHistone demethylase LSD1 plays key roles during carcinogenesis, targeting LSD1 is becoming an emerging option for the treatment of cancers. Numerous LSD1 inhibitors have been reported to date, some of them such as TCP, ORY-1001, GSK-2879552, IMG-7289, INCB059872, CC-90011, and ORY-2001 currently undergo clinical assessment for cancer therapy, particularly for small lung cancer cells (SCLC) and acute myeloid leukemia (AML). This review is to provide a comprehensive overview of LSD1 inhibitors in clinical trials including molecular mechanistic studies, clinical efficacy, adverse drug reactions, and PD/PK studies and offer prospects in this field.

Results of consecutive trials for children newly diagnosed with acute myeloid leukemia from the Australian and New Zealand Children's Cancer Study Group

Blood ◽  
2002 ◽  
Vol 100 (8) ◽  
pp. 2708-2716 ◽  
Author(s):  
Tracey A. O'Brien ◽  
Susan J. Russell ◽  
Marcus R. Vowels ◽  
Cecilia M. Oswald ◽  
Karin Tiedemann ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Allogeneic Bone Marrow Transplantation ◽  
Remission Induction ◽  
Allogeneic Bone ◽  
Newly Diagnosed ◽  
Group 2 ◽  
Acute Myeloid ◽  
Group 1

Despite improvements in the treatment of acute myeloid leukemia (AML), approximately 50% of children die of the disease. Clinical trials in adult patients with AML indicate that idarubicin may have superior efficacy when compared to daunorubicin in the remission-induction phases of chemotherapy. We conducted consecutive clinical trials in children with newly diagnosed AML in which daunorubicin (group 1, n = 102) or idarubicin (group 2, n = 160) was used during the remission-induction (RI) and the early consolidation phases of chemotherapy. Idarubicin was given at a dose of either 10 mg/m2 (group 2A, n = 106) or 12 mg/m2 (group 2B, n = 53). A high rate of RI was achieved for all groups (95% group 1, 90% group 2A, 94% group 2B). There were no significant differences in 5-year event-free survival (EFS) or in overall survival (OS) when the 3 groups were compared (group 1: EFS 50%, OS 56%; group 2A: EFS 50%, OS 60%; group 2B: EFS 34%, OS 50%). RI deaths resulting from treatment toxicity were low—2% for group 1 and 5% for group 2. More gastrointestinal, pulmonary, and renal toxicity but fewer infections were observed in patients receiving idarubicin (P < .001, P = .04,P = .03, respectively). Following RI chemotherapy, all patients received 3 to 4 more courses of identical chemotherapy and then underwent either autologous (n = 156) or an allogeneic bone marrow transplantation (BMT) (n = 35). OS was higher in allogeneic BMT patients than in autologous BMT patients (79% vs 63%;P = .23). We conclude that daunorubicin is as effective as idarubicin for remission-induction therapy for childhood AML and has reduced toxicity.

scholarly journals Remission induction in acute myeloid leukemia

2012 ◽  
Vol 96 (2) ◽  
pp. 164-170 ◽  
Author(s):  
Eytan M. Stein ◽  
Martin S. Tallman
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Remission Induction ◽  
Acute Myeloid

Cladribine in the remission induction of adult acute myeloid leukemia: where do we stand?

2018 ◽  
Vol 98 (3) ◽  
pp. 561-579 ◽  
Author(s):  
Ayman Qasrawi ◽  
Waled Bahaj ◽  
Lien Qasrawi ◽  
Omar Abughanimeh ◽  
John Foxworth ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Remission Induction ◽  
Acute Myeloid

scholarly journals The Expression Changes of CX3CL1 and Interlukin-6 Genes During Remission Induction Therapy in Patients With Acute Myeloid Leukemia

2021 ◽  
Vol 10 ◽  
pp. e2288
Author(s):  
Mahdiyar Iravani Saadi ◽  
Mani Ramzi ◽  
Aliasghar Karimi ◽  
Maryam Owjfard ◽  
Mahmoud Torkamani ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Induction Chemotherapy ◽  
Induction Therapy ◽  
Myeloid Leukemia ◽  
Hematologic Malignancy ◽  
Quantitative Polymerase Chain Reaction ◽  
Remission Induction ◽  
Response To Chemotherapy ◽  
Before And After ◽  
Acute Myeloid

Background: Acute Myeloid Leukemia syndrome (AML) is a hematologic malignancy which is due to clonal extensive proliferation of leukemic precursor cells and is rapidly fatal unless treated or response to chemotherapy. Cytogenetic findings have important role in prognosis and categorization of AML. The aim of this study was to investigate the expression changes in CX3CL1 and Interlukin-6 (IL-6) genes before and after chemotherapy as remission induction therapy in AML patients. Materials and Methods: In this study 69 patients (36 males, 33 female) with AML was selected from tertiary medical heath center. A quantitative polymerase chain reaction (PCR) was done for mRNA expression of CX3CL1 and IL-6genes before and after induction chemotherapy. To obtain expression changes in CX3CL1 and IL-6genes, we used 2-ΔΔCT method. Results: The expression of CX3CL1 and IL-6 was significantly increased after induction chemotherapy. Also, the ΔCt mean of CX3CL1 and IL-6 mRNA was not significant between AML subtype groups. Conclusion: In conclusion, as we showed that chemotherapy significantly increase the expression of CX3CL1 and IL-6 which can be used as a prognostic factor of AML.

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